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Home , Sexual dysfunction

Diagnosis and treatment of Female (FSD)

Results of Topic Selection Process & Next Steps

The nominator, American College of and Gynecology (ACOG) is interested in a new evidence review on Diagnosis and treatment of Female Sexual Dysfunction (FSD) to inform an update of their clinical practice guideline.

We identified 14 recent reviews and a Canadian Guideline covering the scope of this nomination. Therefore, a new review would be duplicative of an existing product. No further activity on this nomination will be undertaken by the Effective Health Care (EHC) Program.

Topic Brief

Topic Number and Name: #0816, Diagnosis and treatment of Female Sexual Dysfunction (FSD)

Nomination Date: 09/05/2018

Topic Brief Date: 3/8/19

Authors Jill Huppert Robin Paynter

Conflict of Interest: None of the investigators have any affiliations or financial involvement that conflicts with the material presented in this report.

1 Background

ACOG is requesting a systematic review to improve the diagnosis and treatment of female sexual dysfunction. The DSM-IV defines female sexual dysfunction (FSD) as any sexual complaint or problem resulting from disorders of desire, arousal, , or sexual pain that causes marked distress or interpersonal difficulty. FSD is estimated to affect between 5-40% of all women, depending on type. 1 In premenopausal women, the prevalence of any FSD may be as high as 40% 2 The major impacts of FSD are on quality of life and relationships. 3

However, the prevalence is just estimated because making the diagnosis of FSD is not standardized. There is not a single, universally accepted diagnostic tool. There are several scales used to measure sexual dysfunction; most assess the four domains (arousal, desire, orgasm, pain); some include additional domains such as satisfaction and lubrication. Most scales were developed about two decades ago. A 2004 literature review (1957 to 2001) yielded 57 questionnaires which assessed sexual function from the patient perspective; 12 were general questionnaires that included some questions in the sexual domain, and 45 were specific to sexual function. 4 In the recent literature, the most commonly used scales are the Female sexual well-being scale (FSWB scale), the Female Sexual Distress Scale (FSDS), the Female Sexual Function Index (FSFI), the Sexual quality of life-female (SQOL-F), Changes in Sexual Functioning Questionnaire-Short-Form (CSFQ-14), and Arizona Sexual Experiences Scale (ASEX).

Additionally, prevalence may be underestimated because there is no accepted guidance for when and how often to screen women for FSD. Some authors recommend using a tool called the Sexual Complaints Screener.5 However, the ACOG Practice Bulletin #119 recommends the use of the Brief Sexual Symptom Checklist 6 for women who present with symptoms or complaints about sexual function, but does not mention screening asymptomatic women. 1 This guideline was written in 2011, and confirmed in 2017, but was not based on a systematic review of the evidence.

In addition to identifying if FSD is present, it is necessary to correctly categorize the type of FSD. Treatment options vary depending on the type of disorder (desire, arousal, orgasm, pain), and include , hormonal and pharmacotherapy, as well as devices and procedures (surgery, laser, cryotherapy). A recent review listed 42 different treatment modalities, including 26 different classes of medications. 7 In addition, several authors have noted a strong effect. 8

The diagnostic dilemma is: when a woman presents to her clinician, what is the best tool to accurately diagnose and classify her sexual dysfunction disorder? Then, once diagnosed, what are the best treatment options for her? Obstacles to diagnosing and treating FSD include a lack of adequate training in the topic, few perceived treatment options, inadequate clinical time to obtain a sexual history, patients' reluctance to initiate the conversation, and the underestimation of the prevalence of sexual dysfunction.

Nominator and Stakeholder Engagement ACOG provided additional details to focus the scope and develop appropriate contextual questions.

Key Questions and PICOs The key questions for this nomination are:

1. What is the performance (comparative performance) of instruments/checklists/ tests to diagnose sexual dysfunction in women who present with symptoms or sexual function complaints?

2 2. What is the effectiveness and comparative effectiveness of interventions (pharmacologic and non-pharmacologic) to treat women with sexual dysfunction?

a. In women with desire disorders? b. In women with arousal disorders? c. In women with orgasmic disorders? d. In women with pain/penetration disorders?

3. What are the harms and comparative harms of interventions (pharmacologic and non- pharmacologic) to treat women with sexual dysfunction?

To define the inclusion criteria for the key questions, we specify the population, interventions, comparators, outcomes, and setting (PICOS) of interest (Table 1).

Table 1: Key Questions and PICOS Key KQ 1: KQ 2: treatment K3: Harms Questions diagnosis Population Sexually active Women with female sexual Women with female sexual women of any dysfunction dysfunction (regardless of age with a. Desire disorders category of dysfunction) suspected b. Arousal disorder female sexual c. Orgasmic disorder Exclude postpartum, partner dysfunction d. Pain/penetration causes disorders Exclude Examine subgroups postpartum Exclude postpartum population; (menopausal status, population; exclude partner causes. predisposing factors such as exclude partner sexual trauma, co-morbidities) causes Examine subgroups (menopausal status, predisposing factors such as sexual trauma, co-morbidities) Interventions • Brief • Medications • Medications Sexual o o Androgens Symptom o o Estrogens Checklist o SSRI (Wellbutrin, etc) o SSRI (Wellbutrin, etc) • Diagnostic o others o others instruments • Behavioral/psychotherapy • Behavioral/psychotherapy • Diagnostic • Physical interventions • Physical interventions tests (pelvic floor physical (pelvic floor physical therapy, dilation, carbon therapy, dilation, carbon dioxide fractional laser dioxide fractional laser treatment, lubricants, etc) treatment, lubricants, etc) • Devices • Devices Comparators Other diagnostic Any other active therapy Any other active therapy instrument or Placebo Placebo test

3 Key KQ 1: KQ 2: treatment K3: Harms Questions diagnosis Outcomes Diagnostic Benefits: Harms: accuracy • Improvement in sexual • related function: (Hirsutism, , o desire virilization) o arousal • Cardiovascular risk o ability to achieve • cancer orgasm • Other o painless intercourse • Improvement in Quality of Life • Resolution of personal distress Timing/Setting Restrict to Very Restrict to Very High Index Restrict to Very High Index High Index Countries Countries Countries Abbreviations: SSRI: selective serotonin receptor inhibitor

Methods

We assessed nomination #0816, Diagnosis and Treatment of Female Sexual Dysfunction (FSD) for priority for a systematic review or other AHRQ EHC report with a hierarchical process using established selection criteria. Assessment of each criterion determined the need to evaluate the next one. See Appendix A for detailed description of the criteria. 1. Determine the appropriateness of the nominated topic for inclusion in the EHC program. 2. Establish the overall importance of a potential topic as representing a health or healthcare issue in the United States. 3. Determine the desirability of new evidence review by examining whether a new systematic review or other AHRQ product would be duplicative. 4. Assess the potential impact a new systematic review or other AHRQ product. 5. Assess whether the current state of the evidence allows for a systematic review or other AHRQ product (feasibility). 6. Determine the potential value of a new systematic review or other AHRQ product.

Appropriateness and Importance We assessed the nomination for appropriateness and importance.

Desirability of New Review/Duplication We searched for high-quality, completed or in-process evidence reviews published in the last three years on the key questions of the nomination. See Appendix B for sources searched and Appendix C for details of the Pubmed search.

Results

See Appendix A for detailed assessments of all EPC selection criteria.

Appropriateness and Importance This is an appropriate and important topic. FSD affects a significant proportion of women in the USA, and there are significant barriers to appropriate diagnosis and treatment. Treatment depends on an accurate diagnosis, and all medical and surgical therapies have associated with benefits and harms. ACOG has a practice bulletin which needs to be updated.

4 Desirability of New Review/Duplication A new evidence review would be duplicative of existing evidence reviews. The Pubmed search uncovered 14 systematic reviews that cover parts of the key questions, and thus would be useful to the nominator. See Table 2, Duplication column.

Table 2. Key Questions and Results for Duplication Key Question Duplication (01/2015-11/2018) KQ 1: Diagnosis of FSD Total number of identified systematic reviews: 1 • One SR limited to 9 • One protocol 10 KQ 2: Treatment of FSD Total number of identified systematic reviews: 17 • Cochrane: 1 11 • Others 7,8,12-24 KQ 3: Harms Total number of identified systematic reviews: 4 • Cochrane: 1 11 • Others: 21-23

Key Question 1: What is the performance (comparative performance) of instruments/checklists/ tests to diagnose sexual dysfunction in women?

We identified one systematic review and five narrative reviews on diagnosis of sexual dysfunction. A recent good quality review searched for instruments to measure sexual desire (one of the 4 domains of sexual functioning). The methodological quality of the instruments was evaluated by the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) checklist. Authors found 15 articles on 10 instruments, search date ended November 2017.9 We found no recent SRs on diagnosis of the other sexual function domains, or measures of overall sexual functioning.

We found 5 recent general reviews that highlight the difficulty of making an accurate diagnosis of FSD. 5,25-28 However, none of these are systematic reviews. An exhaustive search for sexual health questionnaires was published in 2004, encompassing literature from 1957 to 2001.4 In PROSPERO, we found one in-progress 2016 protocol “Measurement properties of instruments for women's sexual health.” We have contacted the primary author (who is based in Iran), but received no response.10

The Society of Obstetricians and Gynecologists of Canada published their 2018 Female Sexual Health Consensus Clinical Guidelines, which included recommendations for diagnosis. 29 The authors state that they performed a literature search through 2010, however, many references list the source as Uptodate.com (not publically available). Evaluation of the quality of evidence and grading of their recommendations was based on the Canadian task force on preventive services.

Key question 2: What is the effectiveness and comparative effectiveness of interventions (pharmacologic and non-pharmacologic) to treat women with sexual dysfunction?

We identified 17 systematic reviews on treatment of sexual dysfunction. See Table 3. • One (the 2018 Female Sexual Health Clinical Consensus Guidelines) reported that their assessment of quality and strength of evidence was based on a systematic review; however, the systematic review details were not provided. 29 • Five systematic reviews focused on women generally o Of these, two recent reviews by Weinberg address effectiveness, but not comparative effectiveness. 7,8 The first highlights the strong placebo effect, and may not be useful to practitioners and patients. 8 The second is of undetermined quality, and the search will be more than three years old by February 2019. 7 o Three other fair quality reviews address the effectiveness of single interventions (DHEA, mindfulness and phosphodiesterase type 5 inhibitors). 5 • Four have searches more than three years old (search ended prior to January 2016). 15,21,22,24 • Seven reviews focused on menopausal women, and five specifically addressed vaginal atrophy (which is a specific subset of pain disorders)11-13,15,19 Two good quality reviews address the effectiveness and comparative effectiveness of hormonal treatment. One is from the Cochrane group 11, and the second includes a metanalysis. 13

• For KQ 2d (sexual pain disorders), we found three reviews. 14,24,30 The broadest of these (any sexual pain disorder) is likely outdated. The most recent is a good quality SR is limited to therapies for women with , and the single outcome is completed vaginal intercourse. 14

• For KQ 2a (desire disorders), we found only one recent good quality review. However, the only intervention studied was topical . 17

We identified two ongoing systematic reviews that may be relevant:

1. Interventions to treat male and female sexual dysfunctions: an overview of systematic reviews. (from the National Health Service of England, posted in 2017)31 Authors indicate that the review will be published in the near future.

2. Absolute/comparative efficacy and tolerability of hormonal and non-hormonal approaches of sexual dysfunctions in postmenopausal women. (from authors in Brazil, posted in 2018) 32 Authors indicate that the review will be publicly available in the near future.

6 Table 3: Summary of 17 recent systematic reviews on treatment (KQ2), sorted by subpopulation. (* denotes outdated search)

Author, Year Search Population Intervention Outcome Details end date (women) Weinberger, Sep All Placebo vs. any FSFI total score MA 2018 8 2016 pharmacotherapy Weinberger, Feb All 42 Treatment Any sexual Study quality 20187 2016 modalities function not assessed, vs. any other SOE not graded Stephenson, March All Mindfulness-based Any sexual Study quality 2017 18 2016 therapy (MBT) function not assessed, MA Gao, 2016 23 Jan 2016 All phosphodiesterase Any sexual Study quality type 5 inhibitors function not assessed, (PDE5is) vs. placebo MA Peixoto, 2017 Aug Men and DHEA Any sexual SOE not 20 2016 women function graded Sauer, 2018 May Meno/ peri- DHEA (intravaginal) , Single 12 2017 menopausal vs. other Sexual function database, with vaginal SOE not atrophy graded Pitsouni, May Menopausal Vaginal estrogens Dyspareunia, MA 2018 13 2017 with vaginal vs. dryness, atrophy non-hormonal or orgasm, sexual hormonal function Lethaby, April Menopausal Topical vs. Dyspareunia Cochrane 2016 11 2016 with vaginal other update atrophy Lee, 2018 15 Mar Menopausal Any medication Dyspareunia Study quality 2015* with vaginal therapy not assessed, atrophy Network MA Pitsouni, October Menopausal Laser therapy vs Dyspareunia, MA 2017 19 2016 women with other sexual dyspareunia satisfaction “2017” Menopausal Fennel (with or Sexual activity, Khadivzadeh, without other dyspareunia 2018 16 therapy) vs. other Achilli, 2017 Oct Menopausal + Transdermal SSE, sexual MA 21 2014* HSDD testosterone vs. activity, placebo , desire Maseroli, Apr 2018 Women with Medical or Completed MA 201814 vaginismus psychosocial penetrative interventions intercourse Morin, 2017 30 Oct 2016 Women with physical therapy Dyspareunia, SOE not provoked modalities vs. other sexual function graded Al-Abbadey, Nov Sexual pain Any therapy Any sexual SOE not 2016 24 2014* disorders function graded Ganesan “2018” HSDD Transdermal Sexual activity Rapid review 2018 17 testosterone vs. or function, other personal Distress Jaspers, 2016 June HSDD vs. other SSE, desire MA 22 2015* Abbreviations: FSFI= Female Sexual Function Index; HSDD= Hypoactive sexual desire disorder; MA= meta-analysis performed; SOE= Strength of Evidence, SSE=Satisfying sexual events,

7 Key question 3: What are the harms and comparative harms of interventions (pharmacologic and non-pharmacologic) to treat women with sexual dysfunction?

We found four SRs that specifically evaluated harms or adverse events associated with therapy for FSD. 11,21-23 Each addressed a single intervention. Achilles (testosterone for desire disorder), Jaspers (flibanserin for desire disorder) and Gao (phosphodiesterase type 5 inhibitors for any FSD) may have outdated searches. The Cochrane review by Lethaby is limited to vaginal estrogens for dyspareunia related to atrophy.

Summary of Findings

• Appropriateness and importance: The topic is both appropriate and important. • Duplication: A new review would be duplicative of existing products.

References

1. Committee on Practice Bulletins-Gynecology. Female Sexual Dysfuntion. Practice Bulletin. 2017;119. https://www.acog.org/-/media/Practice-Bulletins/Committee-on- Practice-Bulletins----Gynecology/pb119.pdf?dmc=1. 2. McCool ME, Zuelke A, Theurich MA, Knuettel H, Ricci C, Apfelbacher C. Prevalence of Female Sexual Dysfunction Among Premenopausal Women: A Systematic Review and Meta-Analysis of Observational Studies. Sex Med Rev. 2016;4(3):197-212. 3. Nappi RE, Cucinella L, Martella S, Rossi M, Tiranini L, Martini E. Female sexual dysfunction (FSD): Prevalence and impact on quality of life (QoL). Maturitas. 2016;94:87-91. 4. Arrington R, Cofrancesco J, Wu AW. Questionnaires to measure sexual quality of life. Qual Life Res. 2004;13(10):1643-1658. 5. Giraldi A, Rellini A, Pfaus JG, et al. Questionnaires for assessment of female sexual dysfunction: a review and proposal for a standardized screener. J Sex Med. 2011;8(10):2681-2706. 6. Hatzichristou D, Rosen RC, Derogatis LR, et al. Recommendations for the clinical evaluation of men and women with sexual dysfunction. J Sex Med. 2010;7(1 Pt 2):337- 348. 7. Weinberger JM, Houman J, Caron AT, Anger J. Female Sexual Dysfunction: A Systematic Review of Outcomes Across Various Treatment Modalities. reviews. 2018. 8. Weinberger JM, Houman J, Caron AT, et al. Female Sexual Dysfunction and the Placebo Effect: A Meta-analysis. Obstetrics and gynecology. 2018;132(2):453-458. 9. Cartagena-Ramos D, Fuentealba-Torres M, Rebustini F, et al. Systematic review of the psychometric properties of instruments to measure sexual desire. BMC medical research methodology. 2018;18(1):109. 10. Sedigheh Moghasemi NRGOAAK. Measurement properties of instruments for women's sexual health: a protocol for systematic review and meta analysis. 11. Lethaby A, Ayeleke RO, Roberts H. Local oestrogen for vaginal atrophy in postmenopausal women. The Cochrane database of systematic reviews. 2016(8):CD001500. 12. Sauer U, Talaulikar V, Davies MC. Efficacy of intravaginal dehydroepiandrosterone (DHEA) for symptomatic women in the peri- or postmenopausal phase. Maturitas. 2018;116:79-82. 13. Pitsouni E, Grigoriadis T, Douskos A, Kyriakidou M, Falagas ME, Athanasiou S. Efficacy of vaginal therapies alternative to vaginal estrogens on sexual function and orgasm of menopausal women: A systematic review and meta-analysis of randomized controlled trials. European journal of obstetrics, gynecology, and reproductive biology. 2018;229:45-56.

8 14. Maseroli E, Scavello I, Rastrelli G, et al. Outcome of Medical and Psychosexual Interventions for Vaginismus: A Systematic Review and Meta-Analysis. The journal of sexual medicine. 2018. 15. Lee A, Kim TH, Lee HH, et al. Therapeutic Approaches to Atrophic in Postmenopausal Women: A Systematic Review with a Network Meta-analysis of Randomized Controlled Trials. Journal of menopausal medicine. 2018;24(1):1-10. 16. Khadivzadeh T, Najafi MN, Kargarfard L, Ghazanfarpour M, Dizavandi FR, Khorsand I. Effect of Fennel on the Health Status of Menopausal Women: A Systematic and Meta- analysis. Journal of menopausal medicine. 2018;24(1):67-74. 17. Ganesan K, Habboush Y, Sultan S. Transdermal Testosterone in Female Hypoactive Sexual Desire Disorder: A Rapid Qualitative Systematic Review Using Grading of Recommendations Assessment, Development and Evaluation. Cureus. 2018;10(3):e2401. 18. Stephenson KR, Kerth J. Effects of Mindfulness-Based Therapies for Female Sexual Dysfunction: A Meta-Analytic Review. Journal of sex research. 2017;54(7):832-849. 19. Pitsouni E, Grigoriadis T, Falagas ME, Salvatore S, Athanasiou S. Laser therapy for the genitourinary syndrome of . A systematic review and meta-analysis. Maturitas. 2017;103:78-88. 20. Peixoto C, Carrilho CG, Barros JA, et al. The effects of dehydroepiandrosterone on sexual function: a systematic review. Climacteric : the journal of the International Menopause Society. 2017;20(2):129-137. 21. Achilli C, Pundir J, Ramanathan P, Sabatini L, Hamoda H, Panay N. Efficacy and safety of transdermal testosterone in postmenopausal women with hypoactive sexual desire disorder: a systematic review and meta-analysis. Fertil Steril. 2017;107(2):475-482 e415. 22. Jaspers L, Feys F, Bramer WM, Franco OH, Leusink P, Laan ET. Efficacy and Safety of Flibanserin for the Treatment of Hypoactive Sexual Desire Disorder in Women: A Systematic Review and Meta-analysis. JAMA Intern Med. 2016;176(4):453-462. 23. Gao L, Yang L, Qian S, Li T, Han P, Yuan J. Systematic review and meta-analysis of phosphodiesterase type 5 inhibitors for the treatment of female sexual dysfunction. Int J Gynaecol Obstet. 2016;133(2):139-145. 24. Al-Abbadey M, Liossi C, Curran N, Schoth DE, Graham CA. Treatment of Female Sexual Pain Disorders: A Systematic Review. Journal of sex & marital therapy. 2016;42(2):99-142. 25. Chedraui P, Perez-Lopez FR. Assessing sexual problems in women at midlife using the short version of the female sexual function index. Maturitas. 2015;82(3):299-303. 26. Mestre M, Lleberia J, Pubill J, Espuna-Pons M. Questionnaires in the assessment of sexual function in women with urinary incontinence and . Actas urologicas espanolas. 2015;39(3):175-182. 27. Hatzichristou D, Kirana PS, Banner L, et al. Diagnosing Sexual Dysfunction in Men and Women: Sexual History Taking and the Role of Symptom Scales and Questionnaires. J Sex Med. 2016;13(8):1166-1182. 28. Parish SJ, Goldstein AT, Goldstein SW, et al. Toward a More Evidence-Based Nosology and Nomenclature for Female Sexual Dysfunctions-Part II. The journal of sexual medicine. 2016;13(12):1888-1906. 29. Lamont J, Bajzak K, Bouchard C, et al. No. 279-Female Sexual Health Consensus Clinical Guidelines. Journal of obstetrics and Canada : JOGC = Journal d'obstetrique et gynecologie du Canada : JOGC. 2018;40(6):e451-e503. 30. Morin M, Carroll M-S, Bergeron S. Systematic Review of the Effectiveness of Physical Therapy Modalities in Women With Provoked Vestibulodynia. Sexual medicine reviews. 2017;5(3):295-322. 31. Ciocanel O, Power K, Eriksen A. Interventions to treat male and female sexual dysfunctions: an overview of systematic reviews. 2017.

9 32. Ana Katherine Gonçalves ASAPFKSdMJCCRNOCJLPCG. Absolute/comparative efficacy and tolerability of hormonal and non-hormonal approaches of sexual dysfunctions in postmenopausal women.

2 Appendix A. Selection Criteria Assessment

Selection Criteria Assessment 1. Appropriateness 1a. Does the nomination represent a health care Yes drug, intervention, device, technology, or health care system/setting available (or soon to be available) in the U.S.? 1b. Is the nomination a request for a systematic Yes review? 1c. Is the focus on effectiveness or comparative Yes effectiveness? 1d. Is the nomination focus supported by a logic Yes model or biologic plausibility? Is it consistent or coherent with what is known about the topic? 2. Importance 2a. Represents a significant disease burden; large FSD affects 5-40% of women in the US proportion of the population

2b. Is of high public interest; affects health care Yes. There are significant barriers to appropriate decision making, outcomes, or costs for a large diagnosis and treatment. proportion of the US population or for a vulnerable population 2c. Represents important uncertainty for decision Yes. Clinicians need guidance to assess patients makers for symptoms. Treatment depends on an accurate diagnosis. 2d. Incorporates issues around both clinical Yes. Medical and surgical therapies are all benefits and potential clinical harms associated with benefits and harms 2e. Represents high costs due to common use, Yes. high unit costs, or high associated costs to consumers, to patients, to health care systems, or to payers 3. Desirability of a New Evidence Review/Duplication 3. Would not be redundant (i.e., the proposed Several recent reviews cover parts of the topic topic is not already covered by available or soon- to-be available high-quality systematic review by AHRQ or others) Abbreviations: AHRQ=Agency for Healthcare Research and Quality; FSD=female sexual dysfunction; KQ=Key Question

A-1

Appendix B. Search for Evidence Reviews (Duplication)

Listed below are the sources searched, hierarchically Primary Search Search results AHRQ: Evidence reports and technology Strategy: sexual assessments 0 https://effectivehealthcare.ahrq.gov/; https://www.ahrq.gov/research/findings/ta/index.html; https://www.ahrq.gov/research/findings/evidence- based-reports/search.html VA Products: PBM, and HSR&D (ESP) publications, Strategy: sexual and VA/DoD EBCPG Program 0 https://www.hsrd.research.va.gov/publications/esp/ Cochrane Systematic Reviews Strategy: sexual http://www.cochranelibrary.com/ One: estrogen for vaginal atrophy HTA (CRD database): Health Technology 0 Assessments http://www.crd.york.ac.uk/crdweb/ PubMed Health http://www.ncbi.nlm.nih.gov/pubmedhealth/ Secondary Search PROSPERO Database (international prospective >10 protocols found, most focused on a single register of systematic reviews and protocols) disease http://www.crd.york.ac.uk/prospero/ Two may overlap: 1. Measurement properties of instruments for women's sexual health (Iran, 2016) 2. Interventions to treat male and female sexual dysfunctions: an overview of systematic reviews (NHS, 2017) Tertiary Search search PubMed https://www.ncbi.nlm.nih.gov/pubmed/ Search string for SR

Search ((((((((sexual[Title/Abstract]) AND function[Title/Abstract])) OR ((sexual[Title/Abstract]) AND dysfunction[Title/Abstract]))) AND ((female[Title/Abstract]) OR women[Title/Abstract])) AND Review[ptyp] AND "last 5 years"[PDat] AND Humans[Mesh] AND English[lang])) NOT cancer[Title/Abstract] Filters: Review; Publication date from 2015/01/01 to 2018/12/31; Humans; English

B-1 Appendix C. Search Strategy & Results (Duplication)

Ovid MEDLINE(R) and Epub Ahead of Print, In-Process & Other Non-Indexed Citations and Daily 1946 to November 26, 2018 Date searched: November 27, 2018 Searched by: Robin Paynter, MLIS

# Searches Results

1 sexual dysfunctions, psychological/ or dyspareunia/ 7602

2 (dyspareunia or (hypoactive* adj2 desire*) or "pain penetration disorder*" or "painful intercourse" 16250 or ((arousal or desire or orgasm* or sexual) adj2 (disorder* or dysfunction*))).ti,ab,kf.

3 or/1-2 19729

4 female/ and humans/ 7082798

5 (female or females or women or woman).ti,ab,kf. 1794346

6 or/4-5 7555122

7 and/3,6 13642

8 Diagnosis/ or di.fs. 2413381

9 (diagnos* or "brief sexual symptom" or checklist* or instrument* or questionnaire*).ti,ab,kf. 2875571

10 or/8-9 4339192

11 and/7,10 6255

12 limit 11 to (adaptive clinical trial or clinical trial, all or controlled clinical trial or equivalence trial or 692 pragmatic clinical trial or randomized controlled trial)

13 limit 12 to yr="2013 -Current" Diagnosis Trials 299

14 limit 13 to english language 290

15 limit 11 to (meta analysis or randomized controlled trial) 341

16 limit 15 to yr="2015 -Current" 95

17 limit 16 to english language Diagnosis and SRs MAs 95

18 Treatment Outcome/ or (dt or px or rh or th).fs. 4959751

19 (androgen* or behavior* or behaviour* or device* or dilat* or drug or drugs or estrogen* or 8948403 intervention* or laser* or lubricant* or lubricat* or medicat* or nonpharmacolog* or non- pharmacolog* or pharmacolog* or psychotherap* or psycho-therap* or SSRI or therap* or treat* or welbutrin).ti,ab,kf.

20 or/18-19 10772776

C-1 # Searches Results

21 and/7,20 11000

22 limit 21 to (adaptive clinical trial or clinical trial, all or controlled clinical trial or equivalence trial or 1223 pragmatic clinical trial or randomized controlled trial)

23 limit 22 to yr="2013 -Current" Treatment Trials 438

24 limit 23 to english language 425

25 limit 21 to (meta analysis or systematic reviews) 652

26 limit 25 to yr="2015 -Current" 245

27 limit 26 to english language Treatment SRs and MAs 230

C-2